Diverse biological activities of moxa extract and smoke.

Diverse biological activities of moxa extracts and smoke (gas phase) were investigated. Moxa was extracted with hot water (Fr. I), or ethanol (Fr. II), or extracted with hot water after ethanol wash (Fr. III) and then lyophilized to obtain the dried powders. Moxa smoke (containing a lot of gaseous components obtained by burning Moxa) (Fr. IV) was collected into phosphate-buffered saline and quantified spectrophotometrically. These extracts and Moxa smoke showed comparable cytotoxic activity against human oral tumor cell lines (HSC-2, HSG). Human gingival fibroblasts (HGF) were more resistant to any Moxa fractions. Neither of the extracts showed anti-HIV activity. Pretreatment of mice with Fr. I significantly reduced the lethal effect of E. coli infection. All extracts produced radicals under alkaline condition, with a maximum intensity at pH 10.5, and enhanced the radical intensity of sodium ascorbate. It was unexpected that these extracts show significant O2- scavenging activities. These data suggest the medicinal efficacy of Moxa extracts and smoke.

Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies.

Mutations of receptor tyrosine kinases are implicated in the constitutive activation and development of human malignancy. An internal tandem duplication (ITD) of the juxtamembrane (JM) domain-coding sequence of the FLT3 gene (FLT3/ITD) is found in 20% of patients with acute myeloid leukemia (AML) and is strongly associated with leukocytosis and a poor prognosis. On the other hand, mutations of the c-KIT gene, which have been found in mast cell leukemia and AML, are clustered in 2 distinct regions, the JM domain and D816 within the activation loop. This study was designed to analyze the mutation of D835 of FLT3, which corresponds to D816 of c-KIT, in a large series of human hematologic malignancies. Several kinds of missense mutations were found in 30 of the 429 (7.0%) AML cases, 1 of the 29 (3.4%) myelodysplastic syndrome (MDS) cases, and 1 of the 36 (2.8%) acute lymphocytic leukemia patients. The D835Y mutation was most frequently found (22 of the 32 D835 mutations), followed by the D835V (5), and D835H (1), D835E (1), and D835N (1) mutations. Of note is that D835 mutations occurred independently of FLT3/ITD. An analysis in the 201 patients newly diagnosed with AML (excluding M3) revealed that, in contrast to the FLT3/ITD mutation (n = 46), D835 mutations (n = 8) were not significantly related to the leukocytosis, but tended to worsen disease-free survival. All D835-mutant FLT3 were constitutively tyrosine-phosphorylated and transformed 32D cells, suggesting these mutations were constitutively active. These results demonstrate that the FLT3 gene is the target most frequently mutated to become constitutively active in AML.